Developmental Changes in the Delayed Rectifier K ⁺ Channels in Mouse Heart

Abstract

Expression of cardiac transient outward current and inwardly rectifying K+ current is age dependent. However, little is known about age-related changes in cardiac delayed rectifier K+ current (IK, with rapidly and slowly activating components, IKr and IKs, respectively). Accordingly, the purpose of the present study was to assess developmental changes in IK channels in fetal, neonatal, and adult mouse ventricles. Three techniques were used: conventional microelectrode to measure the action potential, voltage clamp to record macroscopic currents of IK, and radioligand assay to examine [3H]dofetilide binding sites. The extent of prolongation of action potential duration at 95% repolarization (APD95) by a selective IKr blocker, dofetilide (1 mumol/L), dramatically decreased from fetal (137% +/- 18%) to day-1 (75% +/- 29%) and day-3 (20% +/- 15%) neonatal mouse ventricular tissues (P < .01). Dofetilide did not prolong APD95 in adult myocardium. IKr is the sole component of IK in day-18 fetal mouse ventricular myocytes. However, both IKr and IKs were observed in day-1 neonatal ventricular myocytes. With further development, IKs became the dominant component of IK in day-3 neonates. In adult mouse ventricular myocytes, neither IKr nor IKs was observed. Correspondingly, a high-affinity binding site for [3H]dofetilide was present in fetal mouse ventricles but was absent in adult ventricles. The complementary data from microelectrode, voltage-clamp, and [3H]dofetilide binding studies demonstrate that expression of the IK channel is developmentally regulated in the mouse heart.

Properties of WT and mutant hERG K+ channels expressed in neonatal mouse cardiomyocytes

“…In neonatal mouse cardiomyocytes, native I Kr was identified as an E4031-sensitve current that was small in amplitude (peak tail I Kr ϳ1.6 pA/pF), and our I Kr recordings are similar to those in previous reports (24,27,40,41). WT hERG channel overexpression generated an E4031-sensitive current that activated over a voltage range similar to I Kr but with an amplitude ϳ10-fold greater.…”

Expansion and Differentiation of Germline-Derived Pluripotent Stem Cells on Biomaterials

“…However, beating areas of gPS cells on Resomer LR704 showed slightly shorter APDs than on gelatine, indicating a more mature cardiomyogenic differentiation level. 36 gPS cell-derived cardiomyocytes resemble functionally their ES cell-derived counterparts as reported before. 37 Microarray analysis (Fig.…”

Developmental Toxicity in the Pregnant Rabbit by theClass III Antiarrhythmic Drug Sotalol

“…The Ikr channel is known to be expressed and functional in rodents during the susceptible period, and has been suggested to play a universal important role across species in the embryonic development of the cardiac electrophysiological system (Davies et al 1996;Wang et al 1996). However, in adult rodents, the Ikr channel is superseded by another potassium channel (Ito) during the repolarisation phase (Abrahamsson et al 1994).…”